Canine distemper virus (CDV) is a member of the Morbillivirus genus, which also includes measles virus (MV), rinderpest virus (RPV), peste des petits ruminants virus and morbilliviruses that infect aquatic mammals (Blixenkrone-Moller, 1993; Di Guardo et al., 2005). These related viruses each generally have a restricted natural host range. For example MV infects humans, RPV infects cattle and other even-toed ungulates, and CDV infects a variety of carnivorous animals. However, CDV infection has been observed in monkey colonies indicating that its host range can extend to primates (Qiu et al., 2011; Sakai et al., 2013a), but so far, there is no conclusive evidence linking CDV to human disease in spite of its speculative association to illness of unknown etiology (Rima and Duprex, 2006). Lab-adapted CDV has been injected into humans without causing symptoms of infection suggesting that humans are a non-permissive host for CDV (Hoekenga et al., 1960), which is consistent with recent studies showing that mutations facilitating both entry and replication are needed for CDV to efficiently adapt to human cells (Otsuki et al., 2013; Sakai et al., 2013b). Prevalent MV immunity induced by universal vaccination or natural infections might also play a role in preventing CDV from crossing the human barrier (de Vries et al., 2014). Despite considerable characterization of antigenic and immunological relationships between CDV and MV (Haile et al., 1982; Orvell and Norrby, 1974, 1980; Stephenson and ter Meulen, 1979), CDV neutralizing antibodies (nAbs) in humans have not been extensively investigated.
Morbilliviruses are attractive candidates for development of replication-competent vectors because modified live vaccines (e.g. MV, CDV, and RPV) have proven to be very safe and efficacious (Buczkowski et al., 2014), and promising preclinical results have been generated with a number of experimental vectors (Brandler et al., 2007; Brandler and Tangy, 2008; Despres et al., 2005; Gauvrit et al., 2008; Guerbois et al., 2009; Miest and Cattaneo, 2014; Wang et al., 2012). Morbilliviruses seem particularly relevant for development of replication-competent AIDS vaccine vectors since this genera of viruses replicates in lymphoid tissues like HIV (Draper and Heeney, 2010; Koff et al., 2013; Parks et al., 2013). Pre-existing MV immunity may make the use of MV vectors problematic, and unlike other viral vector systems in which rare serotype viruses can be used as vector alternatives (Mingozzi et al., 2013; Santra et al., 2009), MV has just one serotype. Thus, CDV has been considered as a MV alternative to minimize the effect of widespread anti-MV antibodies (Miest et al., 2011; Zhang et al., 2013b). Because antibodies specific to MV do cross-react with CDV (Appel et al., 1984; de Vries et al., 2014; Rima, 1983; Taylor et al., 1991), it is important to evaluate the prevalence and potency of CDV neutralizing activity in humans.
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